Exploring the Use of the Suzuki Coupling Reaction in the Synthesis of 4′-Alkyl-2′-hydroxyacetophenones

Abstract

International audienceA series of 4′-alkyl-2′-hydroxyacetophenones were prepared by Suzuki cross-coupling reactions of 4′-bromo-2′-hydroxyacetophenone. In these reactions, alkyl(trifluoro)borates were found to be better reactants than alkylboronic acids. 4′-Alkyl-2′-hydroxyacetophenones are key intermediates for the further synthesis of -lipoflavonoids that are more readily incorporated into lipid bilayer membranes than flavonoids and should, therefore, have superior -biological effects through increased bioavailability

A Revised Modular Approach to (–)‐trans‐Δ8‐THC and Derivatives Through Late‐Stage Suzuki–Miyaura Cross‐Coupling Reactions

“…[20] The BF 3 K salts, used as substrates for cross-coupling reactions, were prepared in a straightforward manner from the corresponding boronic acids under non-etching conditions. It was found that Pd(OAc) 2 combined with RuPhos and NaOH facilitated coupling with sp 3 -hybridized reagents with minimal -hydride elimination.…”

“…General procedure III for sp 2 -sp 3 Suzuki Miyaura coupling (12a-12b, 13a-13b): [20] Bromo-(-)-trans-Δ 8 -tetrahydrocannabinol (6)/ (7) (1 equiv.) was dissolved in toluene (0.2M) and Pd(OAc) 2 (10 mol-%), RuPhos (20 mol-%), alkyl trifluoroborate salt (1.5 equiv.)…”

A Revised Modular Approach to D8-THC and Derivatives Through Late-Stage Suzuki-Miyaura Cross-Coupling Reactions

“…It was found that Pd(OAc)2 combined with RuPhos and NaOH facilitated coupling with sp 3 -hybridized reagents with minimal -hydride elimination. 20 The BF3K salts, used as substrates for crosscoupling reactions, were prepared in a straightforward manner from the corresponding boronic acids under non-etching conditions. 21 Elaborating on the essential difference of regioisomers 6 and 7, we converted 7 into naturally occurring  8 -THC (13a) and  8 -propyl-THC (13b) by successful Suzuki-Miyaura cross-coupling (Scheme 5).…”

“…The product was isolated by filtration and the flask and filter were rinsed with n-heptane (4 mL). The filtrated solid was dried under high vacuum and this afforded (20)…”